Table 3.
Parameter estimates obtained from the population pharmacokinetic model stratified by disease state.
| Description of PK Parameter | PK Parameter | Healthy | NASH | Difference | p-value |
|---|---|---|---|---|---|
| Uptake clearance from blood to liver | CLuptake (L/min) | 1.14 (0.732–2.27) |
0.731 (0.382–1.04) |
−0.398 [−0.679, −0.202] |
0.0008* |
| Efflux clearance from liver to blood | CLefflux (L/min) | 0.00800 (0.00481–0.0139) |
0.00579 (0.00475–0.00903) |
−0.00192 [−0.00384, 0.000137] |
0.0667 |
| Clearance from liver to bile | CLbile (L/min) | 0.0354 (0.0157–0.0728) |
0.0171 (0.0110–0.0207) |
−0.0172 [−0.0268, −0.00467] |
0.0005* |
| Uptake clearance from blood to the peripheral compartment | CLuptake,peripheral (L/min) | 0.754 (0.353–1.01) |
0.491 (0.317–0.811) |
−0.118 [−0.372, 0.0780] |
0.322 |
| Efflux clearance from the peripheral compartment to blood | CLefflux,peripheral (L/min) | 0.00517 (0.00434–0.00708) |
0.00418 (0.00311–0.00555) |
−0.000980 [−0.00175, −0.000356] |
0.004* |
| Central volume of distribution | Vcentral (L) | 11.1 (9.55–12.5) |
6.32 (5.69–9.69) |
−4.42 [−5.54, −3.24] |
<0.0001* |
| Volume of distribution in the liver | Vliver (L) | 0.958 (0.527–1.39) |
0.891 (0.648–1.43) |
−0.0424 [−0.355, 0.225] |
0.913 |
Data presented as median (range). Median difference with 95% confidence interval (by Hodges-Lehmann estimation). Mann-Whitney-Wilcoxon test, NASH vs. healthy,
*
p<0.05